The objective of the proposed research is to illuminate the mechanisms by which mechanical stresses influence the differentiation, growth, organization and adaptation of connective tissue structures, in particular, of artery walls. It is our plan to utilize several model systems which have been developed in our laboratory to characterize the metabolic and biosynthetic responses of connective tissue cells toward biomechanical environmental factors. The first model is one in which arterial smooth muscle cells, fibroblasts, or chondrocytes which are cultured on elastin membranes are induced to modulate their biosynthetic response by cyclic stretching of the membranes. The second system likewise utilizes smooth muscle cells or chondrocytes grown upon elastin membranes but applies an electric field in which frequency and current density are variables. The third system employs surviving cartilage segments mounted in an apparatus designed to apply defined compressive stresses and to study metabolic response. In these systems, responses will be generally monitored with respect to cytoarchitecture, lipid metabolism and the biosynthesis of extracellular macromolecules such as collagen, elastin, proteoglycosaminoglycans and the roles of ionic and hormonal mediators.